WNT receptors profile expression in mature blood cells and immature leukemic cells: RYK emerges as a hallmark receptor of acute leukemia

WNT receptors profile expression in mature blood cells and immature leukemic cells: RYK emerges as a hallmark receptor of acute leukemia
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DOI:
10.1111/ejh.12698
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发表时间:
2016-08-01
影响因子:
3.1
通讯作者:
Jave-Suarez, Luis F.
Jave-Suarez, Luis F.
中科院分区:
医学3区
文献类型:
--
作者:
Alvarez-Zavala, Monserrat;Riveros-Magana, Alma R.;Jave-Suarez, Luis F.

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背景:Wnt 信号传导诱导大量细胞内反应,决定正常或异常的细胞行为。 WNT 信号传导异常与白血病发生过程的发展有关。在这方面,了解正常和恶性细胞中 WNT 受体的表达谱非常重要,以便了解控制细胞行为的 WNT 机制。这项工作旨在确定正常细胞和白血病细胞中 WNT 受体的表达谱。方法:使用来自健康志愿者和急性白血病患者的白血病衍生细胞系、外周血细胞和骨髓样本,通过流式细胞术测定 WNT 受体的表达。结果:尽管成熟正常血细胞和未成熟致瘤细胞中存在异源 WNT 受体表达,但发现 RYK 受体在白血病细胞中高表达,但在正常细胞中不表达。 RYK 表达主要存在于 CD33、CD13、CD7 和 CD117 等未成熟标记物阳性的细胞中。结论:我们的数据显示 T 和 B 白血病细胞之间的 FZD 受体表达存在差异,但这两种细胞类型以及成髓细胞衍生的细胞都表达高水平的 RYK。 RYK 表达与未成熟标志物的关联表明其可能用作诊断标志物或治疗靶点。
Background: Wnt signaling induces a plethora of intracellular responses that dictate normal or abnormal cellular behavior. Abnormal WNT signaling has been related to the development of leukemogenic processes. In this regard, it is important to know the expression profile of WNT receptors in normal and malignant cells, in order to understand the WNT mechanisms that control the cell behavior. This work aimed to determine the WNT receptors expression profile in normal and leukemia cells. Methods: Expression of WNT receptors was determined by flow cytometry using leukemia-derived cell lines, peripheral blood cells, and blood marrow samples from healthy volunteers and acute leukemia patients. Results: Despite the heterogenic WNT receptors expression in mature normal blood cells and in immature tumorigenic cells, the RYK receptor was found highly express in leukemia cells, but not in normal cells. RYK expression was found mainly in cells positive to immature markers like CD33, CD13, CD7, and CD117. Conclusions: Our data show differences in FZD receptors expression between T and B leukemic cells, but both cell types and also myeloblast-derived cells express high levels of RYK. The association of RYK expression with immature markers indicates its possible use as a diagnostic marker or therapeutic target.